ABSTRACT Chronic HIV infection is a 21st century phenomenon due to highly-effective medications called antiretroviral therapies (ART). Because of ART, people living with HIV infection are surviving to older ages when they are at risk for Alzheimer?s Disease and Related Dementias (ADRD). This has never been seen before. People living with HIV also experience cognitive problems and more nervous system illnesses related to the HIV infection. Women, in particular, are at higher vascular risk due to obesity and smoking, as well as certain types of ART that increase vascular risk. High vascular risk is related to ADRD. Identification of blood biomarkers that can tell us something about a person?s risk for ADRD is very important. A simple blood test will also help us better understand ADRD brain pathologies, or changes that lead to memory loss and clinical AD. Two of these pathologies are related to abnormal proteins in the brain, called amyloid and tau, and a third, is called neurodegeneration, or brain cell death. Vascular disease (blood vessel and circulation changes) is also common. Because women with HIV infection are already at high risk, exploring biomarkers of neurodegeneration and vascular health is paramount to understanding associations between HIV infection and ADRD, as well as cognitive impairments that come before ADRD. Candidate, state-of-the-art blood ADRD biomarkers include amyloid (A) proteins called Abeta-40 and Abeta42, and protein markers of brain damage called total tau (t-tau), phospho-tau (p-tau), and NeuroFilament Light chain (NFL). These biomarkers are usually measured in cerebrospinal fluid, the watery fluid that bathes the brain. Recent studies suggest that blood levels of these biomarkers may mirror levels observed in cerebrospinal fluid and are related to brain changes that occur in AD patients, such as brain shrinking due to nerve cell death, and other changes that may result from vascular disease. We have the great opportunity to explore repeated measures of these ADRD biomarkers Abeta-40, Abeta-42, t-tau, p-tau, and NFL, in association with cognition over 10 years in 390 women, who are at least 45 years old - 260 surviving with HIV infection and a comparison group of 130 uninfected women. This is an age when if AD were to develop, Abeta and tau would initially start to accumulate slowly and silently. We propose to use historical data from the MACS/WIHS Combined Cohort Study (MWCCS) WIHS women. In 2019, WIHS women were average 53 years old with measures of social, demographic, clinical, neurological and vascular outcomes, other illnesses, and risk factors, and ART use, as well as stored blood collected over time. In 2009, WIHS began cognitive measures every 2 years to measure different types of thinking, as well as global thinking. For the first time, we will link ADRD blood biomarkers to cognition over time in women with and without HIV infection. This will advance our understanding of brain aging in HIV.